The compounds mentioned above often present 2 or 3 of the activities mentioned above, which confer advantageous pharmacological properties on them.
In fact, taking into account the potential role of the MAO's and ROS's (“reactive oxygen species”, at the origin of lipidic peroxidation) in physiopathology, the new described derivatives corresponding to general formula (I) can produce beneficial or favorable effects in the treatment of pathologies where these enzymes and/or these radicular species are involved. In particular:                disorders of the central or peripheral nervous system such as for example neurological diseases where Parkinson's disease, cerebral or spinal cord traumatisms, cerebral infarction, sub arachnoid hemorrhage, epilepsy, ageing, senile dementia, Alzheimer's disease, Huntington's chorea, amyotrophic lateral sclerosis, peripheral neuropathies, pain can in particular be mentioned;        schizophrenia, depressions, psychoses;        disorders of the memory and the humour;        pathologies such as for example migraine;        behavioural disorders, bulimia and anorexia;        auto-immune and viral diseases such as for example lupus, AIDS, parasitic and viral infections, diabetes and its complications, multiple sclerosis.        addiction to toxic substances;        proliferative and inflammatory pathologies;        and more generally all the pathologies characterised by an excessive production of ROS's and/or participation of MAO's.        
In all of these pathologies, experimental evidence exists which demonstrates the involvement of ROS's (Free Radic. Biol. Med. (1996) 20, 675-705; Antioxid. Health. Dis. (1997) 4 (Handbook of Synthetic Antioxidants), 1-52) as well as the involvement of MAO's (Goodman & Gilman's: The pharmacological basis of therapeutics, 9th ed., 1995, 431-519).
The advantage of a combination of the inhibitory activities of MAO and inhibition of lipidic peroxidation is for example well illustrated in Parkinson's disease. This pathology is characterized by a loss of dopaminergic neurons of the nigrostriatal route the cause of which would in part be linked to an oxidizing stress due to ROS's. The exogenic dopamine from L Dopa is used in therapeutics in order to maintain sufficient levels of dopamine. MAO inhibitors are also used with L Dopa to avoid its metabolic degradation but do not act on the ROS's. Compounds which act both on MAO's and ROS's will therefore have a certain advantage.
Moreover, the character of the modulator of the sodium channels is very useful for therapeutic indications such as:                the treatment or prevention of pain, and in particular:                    post-operative pain,            migraine,            neuropathic pain such as trigeminal neuralgia, post-herpetic pain, diabetic neuropathies, glossopharyngeal neuralgias, secondary radiculopathies and neuropathies associated with metastatic infiltrations, adiposis dolorosa and pain associated with burns,            central pain as a result of vascular cerebral accidents, thalamic lesions and multiple sclerosis, and            chronic inflammatory pain or pain linked to a cancer;                        the treatment of epilepsy;        the treatment of disorders linked to neurodegeneration, and in particular:                    vascular cerebral accidents,            cerebral traumatism, and            neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis;                        the treatment of bipolar disorders and irritable colon syndrome.        
The concrete advantages of the presence in a compound of at least one of these activities is therefore clearly apparent from the above.
The European Patent Application EP 432 740 describes derivatives of hydroxyphenylthiazoles, which can be used in the treatment of inflammatory diseases, in particular rheumatic diseases. These derivatives of hydroxyphenylthiazoles show properties of trapping free radicals and inhibitors of the metabolism of arachidonic acid (they inhibit lipoxygenase and cyclooxygenase).
Other derivatives of hydroxyphenylthiazoles or hydroxyphenyloxazoles are described in the PCT Patent Application WO 99/09829. These have analgesic properties.
A certain number of derivatives of imidazoles with close or identical structures to those of the compounds corresponding to general formula (I) according to the invention have moreover been described by the Applicant in the PCT Patent Application WO 99/64401 as agonists or antagonists of somatostatin. However, said derivatives of imidazoles have therapeutic properties in fields different from those indicated above (suppression of the growth hormone and the treatment of acromegalia, treatment of the recurrence of stenosis, inhibition of the secretion of gastric acid and prevention of gastrointestinal bleeding in particular).
Moreover, the compounds of general formula (A1)
in whichR1 represents one of the aryl, heteroaryl, aralkyl or cycloalkyl radicals optionally substituted by one to three substituents chosen independently from a halogen atom, the CF3, CN, OH, alkyl or alkoxy radical, SO2R9 with R9 representing NH2 or NHCH3;X represents NR2, R2 representing H or alkyl;Y represents N or CR3;Z represents CR3 or N;on the condition however that Y and Z are not both CR3 or N at the same time;R3 represents H, alkyl, halogen, hydroxyalkyl or phenyl optionally substituted by 1 to 3 substituents chosen from H, CF3, CN, SO2NH2, OH, alkyl or alkoxy;m represents 0, 1 or 2;R4 represents H or alkyl;when Z represents CR3, then R3 and R4 can also represent together —(CH2)n1— with n1 an integer from 2 to 4 or R2 and R4 can also represent together —(CH2)n2— with n2 an integer from 2 to 4;R5 and R6 represent independently H, alkyl, alkoxy, aryl or aralkyl;NR5R6 can also represent together (in particular):                the optionally substituted 2-(1,2,3,4-tetrahydroquinolyl) radical,        a        
radical in which R7 represents one of the phenyl, benzyl or phenethyl radicals in which the phenyl ring can be substituted;                a        
radical in which p is an integer from 1 to 3,W is N and R8 represents H, CF3, one of the phenyl, pyridyl or pyrimidinyl radicals optionally substituted once to twice by radicals chosen from halogen, OH, alkyl or alkoxy, orW is CH and R8 represents phenyl optionally substituted or aralkyl optionally substituted on the aryl group;have been described in the PCT Patent Application WO 96/16040 as partial agonists or antagonists of the dopamine sub-receptors of the brain or as prodrug forms of such partial agonists or antagonists. Therefore these compounds would have useful properties in the diagnosis and treatment of affective disorders such as schizophrenia and depression as well as certain disorders of movement such as Parkinson's disease.
It has also been described in the PCT Patent Application WO 98/27108 that certain amides of general formula (A2)
in which:R1 represents in particular an alkyl, optionally substituted phenyl or optionally substituted heterocyclic aryl radical;R2 represents H or phenylalkyl;R4 represents H, quinolyl, 3-4-methylenedioxyphenyl or one of the phenyl or pyridyl radicals optionally substituted, by a radical or radicals chosen in particular from alkyl, alkoxy, alkylthio, optionally protected hydroxy, amino, alkylamino, dialkylamino;R5 represents H or an imidazolyl, phenyl, nitrophenyl, phenylalkyl radical, or also a —CO—N(R7)(R8) radical, in which R7 and R8 represent independently H, phenyl, phenylalkyl, alkyl or alkoxy;or R4 and R5 in combination form a group of formula —CH═CH—CH═CH—;Y is a phenylene radical substituted by a phenyl, phenoxy or phenylalkoxy radical, or a group of formula —CH(R3)-, in which R3 represents H or a radical of formula —(CH2)n—R6, in which R6 represents an optionally protected hydroxy, acyl, carboxy, acylamino, alkoxy, phenylalkoxy, alkylthio, optionally substituted phenyl, optionally substituted pyridyl, pyrazinyl, pyrimidinyl, furyl, imidazolyl, naphthyl, N-alkylindolyl or 3,4-methylenedioxyphenyl radical and n is an integer from 0 to 3;R2 and R3 taken together with the carbon atoms which carry them can form a phenyl group;X represents S or NR9;R9 representing H, an alkyl or cycloalkyl radical, or also a benzyl radical optionally substituted once on its phenyl part by H, alkyl or alkoxy;are inhibitors of the NO synthases and can be used to treat diseases which include in particular cardiovascular or cerebral ischemia, cerebral hemorrhage, disorders of the central nervous system, Alzheimer's disease, multiple sclerosis, diabetes, hepatitis, migraine, rheumatoid arthritis and osteoporosis.
In a different field, the Applicant has itself previously described in the PCT Patent Application WO 98/58934 derivatives of amidines having the ability to inhibit NO synthases and/or lipidic peroxidation.
The Applicant has now unexpectedly discovered that certain intermediates of the first stages of synthesis of the amidines described in the PCT Patent Application WO 98/58934, and more generally certain derivatives of heterocycles with five members, namely the products of general formula (I) defined hereafter, have at least one of the three properties chosen from the following properties (and often even two of these three properties even sometimes all three at the same time):                MAO inhibition properties;        lipidic peroxidation inhibition properties; and        properties of modulating the sodium channels.        
These advantageous properties offer the advantage of opening up numerous uses for such compounds, in particular in the treatment of neurodegenerative diseases, and in particular those indicated previously, of pain or of epilepsy.